POC proposes to develop a new class of submicroscopic chemical sensors for use in the investigation of cellular physiology. These sensors, which can have characteristic dimensions much smaller than 1 micromole, have the potential for monitoring ionic concentrations, enzyme levels, drug concentrations, and a wide variety of other intracellular chemical properties, with relative ease to the researcher. In the proposed approach, chemically sensitive indicators are immobilized by photopolymerization at the tip of finely tapered optical fibers similar to those used in Near-field Scanning Optical Microscopy (NSOM). The technique could thus combine the ultrafine resolution of NSOM with the sensitivity and specificity of active fiber optic chemical sensors. These sensors will offer significant advantages, including faster response time and minimization of cellular damage, over existing physiological microsensors. During Phase I of the project, POC demonstrated the practicality of this technique by fabricating and testing sensors capable of measuring intracellular pH, calcium ion concentration, sodium ion concentration, and potassium ion concentration. Phase II will see the development of a compact system capable of serving as the basis for a line of commercial submicroscopic sensing products, as well as development of new sensor-tip chemistries both to improve the manufacturability and performance of the tips and to increase the number and types of analytes that can be measured. PROPOSED COMMERCIAL APPLICATION: These sensors will find applications in fields as disparate as fundamental cellular neurophysiology and single- cell drug testing. Beginning with products designed for use in academic and National research laboratories, commercialization of near field optical sensors could ultimately lead to their use in pharmaceutical testing, biotechnology development and process control, and even medical diagnosis and pathology.